阿加曲班对MCAO大鼠不同时间点血小板功能的影响

建立大脑中动脉闭塞(model of middle cerebral artery occlusion,MCAO)大鼠模型,研究阿加曲班对大鼠不同时间脑缺血再灌注损伤血小板功能的影响。将120只健康雄性SD大鼠随机分为假手术组(Sham)、模型组(Model)和阿加曲班给药组(Argatroban),其中Argatroban组分为4组:Argatroban+30 min组、Argatroban+1 h组、Argatroban+3 h组和Argatroban+7 h组,Sham组和Model组40只,其余各组每组10只。线栓法制备大鼠MCAO模型,术中输注Argatroban,剂量为0.3μg·kg^-1·min^-1,完成手术前5 min停止输注。手术完成后,Sham组和Model组分别于术后30 min、1 h、3 h和7 h处死10只取样;Argatroban给药组5个时间点处死取样。检测大鼠血浆血细胞数量,并计数骨髓有核细胞数的变化。采用流式细胞仪检测血小板-白细胞聚集体(platelet-leukocyte aggregates,PLA)表达水平,观察活化部分凝血活酶时间(activated partial thromboplastin time,APTT)、血小板计数变化,ELISA检测血浆D-二聚体和TAT。结果显示,与Sham组相比,Model组大鼠的红细胞(RBC)、白细胞(WBC)、血红蛋白含量(HGB)和中性粒细胞(GR)数都显著升高(p<0.05),且与给药组没有统计学差异。Sham组、Model组和Argatroban给药组的骨髓有核细胞数也没有统计学差异。与Sham组相比,Model组PLA表达水平极显著升高(p<0.01),Argatroban+30 min组PLA表达水平却低于Sham组,但没有统计学差异,Argatroban+1 h组高于Sham组和Argatroban+30 min组(p<0.05),Argatroban+3 h组和Argatroban+7 h组高于Argatroban+1 h组低于Sham组。术后各组的血小板计数均高于Sham组(p<0.05),Argatroban各组的血小板计数要低于Model组(p<0.05),并在30 min时达到最低,30 min以后血小板升高,但是1 h以后血小板不再升高,趋于稳定。Argatroban各组PT和APTT虽略有降低,但是与Sham组和Model组并没有统计学差异。造模后各组TAT、D-二聚体水平显著升高,Argatroban各组TAT水平较模型组明显降低(p<0.05),Argatroban+30 min组水平最低。MCAO模型大鼠血液呈现高凝状态,凝血功能和纤维蛋白溶解功能亢进,血小板活化增强,阿加曲班可对此起到改善作用。     

ADAMTSL6β promotes fibrillin‐1 microfibril assembly,which is possibly mediated via binding through the third thrombospondin type I domain to fibrillin‐1

Fibrillin‐1 is the major component of extracellular matrix microfibrils. Microfibrils dysfunction is responsible for the onset of various connective tissue diseases, including Marfan syndrome. Although ADAMTSL (a disintegrin and metalloproteinase with thrombospondin motifs‐like) 6β is one of the fibrillin‐1 binding proteins, the detailed mechanism underlying the involvement of ADAMTSL6β in microfibril formation remains unclear. In this study, we created deletion mutants of ADAMTSL6β and examined their interactions with fibrillin‐1 assembly. Pull‐down assay of the ADAMTSL6β deletion mutants and fibrillin‐1 protein revealed that ADAMTSL6β binds to fibrillin‐1 through the third thrombospondin type I domain. Furthermore, we observed that formation of fibrillin‐1 matrix assembly was enhanced in MG63 cells, expressing full‐length ADAMTSL6β, when compared with that of wild type MG63 cells. While MG63 cells expressing Δ TSP3‐ADAMTSL6β form showed enhanced assembly formation, Δ TSP2‐ADAMTSL6β form did not enhance that, indicating the difference between Δ TSP2‐Δ TSP3 has a critical role for fibrillin‐1 assembly. As the difference of Δ TSP2‐Δ TSP3 is the third thrombospondin type I domain, we concluded that the third thrombospondin type I domain of ADAMTSL6β influence the microfibril formation. Our data are the functional presentation of the biological role of ADAMTSL6β in the process of microfibril formation.     

Dietary GABA induces endogenous synthesis of a novel imidazole peptide homocarnosine in mouse skeletal muscles

Amino Acids - Carnosine (β-alanyl-l-histidine) is an imidazole dipeptide present at high concentrations in skeletal muscles, where it plays a beneficial role. However, oral intake of carnosine...     

UDP‐Api/UDP‐Xyl synthases affect plant development by controlling the content of UDP‐Api to regulate the RG‐II‐borate complex

Rhamnogalacturonan‐II (RG‐II) is structurally the most complex glycan in higher plants, containing 13 different sugars and 21 distinct glycosidic linkages. Two monomeric RG‐II molecules can form an RG‐II‐borate diester dimer through the two apiosyl (Api) residues of side chain A to regulate cross‐linking of pectin in the cell wall. But the relationship of Api biosynthesis and RG‐II dimer is still unclear. In this study we investigated the two homologous UDP‐D‐apiose/UDP‐D‐xylose synthases (AXSs) in Arabidopsis thaliana that synthesize UDP‐D‐apiose (UDP‐Api). Both AXSs are ubiquitously expressed, while AXS2 has higher overall expression than AXS1 in the tissues analyzed. The homozygous axs double mutant is lethal, while heterozygous axs1/+ axs2 and axs1 axs2/+ mutants display intermediate phenotypes. The axs1/+ axs2 mutant plants are unable to set seed and die. By contrast, the axs1 axs2/+ mutant plants exhibit loss of shoot and root apical dominance. UDP‐Api content in axs1 axs2/+ mutants is decreased by 83%. The cell wall of axs1 axs2/+ mutant plants is thicker and contains less RG‐II‐borate complex than wild‐type Col‐0 plants. Taken together, these results provide direct evidence of the importance of AXSs for UDP‐Api and RG‐II‐borate complex formation in plant growth and development.     

Mutation of the chloroplast‐localized phosphate transporter OsPHT2;1 reduces flavonoid accumulation and UV tolerance in rice

Phosphorus (P) is an essential macronutrient required for plant development and production. The mechanisms regulating phosphate (Pi) uptake are well established, but the function of chloroplast Pi homeostasis is poorly understood in Oryza sativa (rice). PHT2;1 is one of the transporters/translocators mediating Pi import into chloroplasts. In this study, to gain insight into the role of OsPHT2;1‐mediated stroma Pi, we analyzed OsPHT2;1 function in Pi utilization and photoprotection. Our results showed that OsPHT2;1 was induced by Pi starvation and light exposure. Cell‐based assays showed that OsPHT2;1 localized to the chloroplast envelope and functioned as a low‐affinity Pi transporter. The ospht2;1 had reduced Pi accumulation, plant growth and photosynthetic rates. Metabolite profiling revealed that 52.6% of the decreased metabolites in ospht2;1 plants were flavonoids, which was further confirmed by 40% lower content of total flavonoids compared with the wild type. As a consequence, ospht2;1 plants were more sensitive to UV‐B irradiation. Moreover, the content of phenylalanine, the precursor of flavonoids, was also reduced, and was largely associated with the repressed expression of ADT1/MTR1. Furthermore, the ospht2;1 plants showed decreased grain yields at relatively high levels of UV‐B irradiance. In summary, OsPHT2;1 functions as a chloroplast‐localized low‐affinity Pi transporter that mediates UV tolerance and rice yields at different latitudes.     

基于功能性状的水杉原生母树种群生境适应策略

植物的功能性状变异和表型可塑性是其应对异质生境的主要机制, 对植物的生长和分布有重要贡献。本文以湖北星斗山国家级自然保护区的水杉(Metasequoia glyptostroboides)原生母树为研究对象, 分析了母树种群功能性状对树木形态、地形因子及人为干扰的响应机制。结果表明: 水杉原生母树叶面积、叶干重和比叶面积的变异幅度大, 可塑性较强, 而枝和叶的干物质含量稳定性最高。人为干扰和4个地形因子均对每个功能性状变异方差有5%-20%的解释度, 冠幅对枝、叶干物质含量的变异方差有高达38%和76%的解释度。5个功能性状主要受海拔、坡位和人为干扰影响, 其中, 比叶面积对环境因子和干扰的响应规律不明显, 叶面积和叶干重在强烈人为干扰的环境中普遍增大, 枝和叶的干物质含量对坡向的变化最敏感。总之, 水杉原生母树种群通过功能性状变异对环境能产生一定的可塑性响应, 但人为干扰对母树生长影响较大, 建议人工辅助更新, 并适度减少农业和建筑对现存母树的影响。     

光氮互作对闽楠幼苗叶片光合生理特性的影响

以5月龄闽楠幼苗为材料,采用4种光照水平(100%、41.3%、14.3%、3.6%自然光)和4种氮素水平(0、0.5、1、2 mol/L纯氮)的双因素盆栽试验,研究光氮互作下闽楠幼苗的光合生理特性,以探讨其对环境适应性的生理机制。结果表明:(1)遮荫和施氮均能显著提高闽楠叶片光合色素含量;在同一氮素水平下,随光照强度下降,闽楠幼苗叶片可溶性糖(SS)、可溶性蛋白(SP)、净光合速率(P_n)、气孔导度(G_s)、最大净光合速率(P_(max))、暗呼吸速率(R_d)、表观量子系数(AQY)均呈先增后降趋势,并在41.3%自然光照水平时最高;而同期叶片胞间CO_2浓度(C_i)、蒸腾速率(T_r)、光饱和点(LSP)、光补偿点(LCP)均呈下降趋势;闽楠幼苗的叶片PSⅡ最大光化学效率(F_v/F_m)和PSⅡ潜在活性(F_v/F_o)则随光照减弱逐渐增加。(2)同一光照水平下,随着氮素施用量增加,闽楠幼苗叶片SS、SP、光合气体交换参数、光响应曲线特征参数总体呈现先升高后降低的趋势,F_v/F_m和F_v/F_o呈先降后增趋势。(3)不同光照和氮素水平之间存在显著的互作效应,隶属函数分析结果以41.3%自然光照、0.5 mol/L纯N处理的效果最优。研究表明,闽楠幼苗为喜光耐荫植物;适宜遮荫和施氮处理组合可显著改善闽楠渗透调节能力,提高光能利用率,促进光合作用进行,而全光照、过度遮荫、缺氮、或过量施氮均不利于闽楠正常生理代谢。     

Targeting P2 receptors in purinergic signaling: a new strategy of active ingredients in traditional Chinese herbals for diseases treatment

Adenosine triphosphate (ATP) and its metabolites adenosine diphosphate, adenosine monophosphate, and adenosine in purinergic signaling pathway play important roles in many diseases. Activation of P2 receptors (P2R) channels and subsequent membrane depolarization can induce accumulation of extracellular ATP, and furtherly cause kinds of diseases, such as pain- and immune-related diseases, cardiac dysfunction, and tumorigenesis. Active ingredients of traditional Chinese herbals which exhibit superior pharmacological activities on diversified P2R channels have been considered as an alternative strategy of disease treatment. Experimental evidence of potential ingredients in Chinese herbs targeting P2R and their pharmacological activities were outlined in the study.